Clinical Outcomes and Immune Metrics in Intratumoral Basophil-Enriched Gastric Cancer Patients

Abstract

Background: Accumulation of basophils has been reported in several malignancies. In gastric cancer, the relation between tumor-infiltrating basophils and patient overall survival and chemotherapeutic responsiveness still remains obscure.

Objective: We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer.

Methods: The study enrolled two independent patient data sets with 448 gastric cancer patients overall. Basophils were evaluated with the use of immunohistochemistry (IHC) staining, and the correlation with clinicopathological characteristics, survival outcomes, and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) were investigated. Additionally, IHC was applied to characterize immune contexture in gastric cancer.

Results: In either the discovery or validation data sets, accumulated basophils indicated poorer prognosis, and tumor-infiltrating basophils were identified as an independent adverse prognostic factor by multivariate analysis. Furthermore, tumor-infiltrating basophils determined significantly inferior therapeutic responsiveness to fluorouracil-based ACT in patients with stage III tumors. In addition, the abundance of basophils was correlated with an immunoevasive contexture characterized by M2-polarized macrophage infiltration. Moreover, our findings indicated elevated interleukin-4 expression but decreased interferon-γ expression in the high-basophils subgroup.

Conclusions: Tumor-infiltrating basophils in gastric cancer were identified as an independent adverse prognosticator, and also predicted inferior chemotherapeutic responsiveness, which identified those patients in need of much more individualized postoperative adjuvant therapy and more stringent follow-up. Furthermore, the infiltration of basophils was associated with immunoevasive tumor microenvironment, which might be a potential immunotherapeutic target for gastric cancer.